The aim of this study was to investigate the clinicopathologic features, treatment and outcome of seven patients with an ovarian Sertoli-Leydig cell tumor (SLCT). Five patients presented with feminization, two with accompanying virilization. One presented with amenorrhea alone. Three of the five patients showing feminization symptoms had endocrine-related diseases. Histologically, five tumors were well differentiated, the other two were poorly differentiated. The latter two patients were misdiagnosed as having an ovarian epithelial carcinoma or granulosa cell tumor from frozen sections. Immunohistochemistry showed that the tumors were calretinin-positive in two patients and one was inhibin-positive. Four patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy(TAH/BSO) and two were treated by unilateral salpingo-oophorectomy. Among them, two patients received adjuvant chemotherapy. Six patients were free of disease in a follow-up of 2-34 years and one achieved a pregnancy. The remaining patient recurred 4 years later. Feminization as well as virilization might provide important clues for a preoperative diagnosis. Histological misdiagnosis is probable in poorly differentiated tumors. Conservative surgery including retention of fertility can be considered. However, the tendency for recurrence in poorly differentiated tumors should be considered.

Background Our laboratory previously reported an individual-level prognostic signature for patients with stage II colorectal cancer (CRC). However, this signature was not applicable for RNA-sequencing datasets. In this study, we constructed a robust epithelial-to-mesenchymal transition (EMT)- related gene pair prognostic signature. Methods Based on EMT-related genes, metastasis-associated gene pairs were identified between metastatic and non-metastatic samples. Then, we selected prognosis-associated gene pairs, which were significantly correlated with disease-free survival of stage II CRC using multivariate Cox regression model, as the EMT-related prognosis signature. Results An EMT-related signature composed of fifty-one gene pairs (51-GPS) for prediction-relapse risk of patients with stage II CRC was developed, whose prognostic efficiency was validated in independent datasets. Moreover, 51-GPS achieved better predictive performance than other reported signatures, including a commercial signature Oncotype Dx colon cancer and an immune-related gene pair signature. Besides, EMT-related functional gene sets achieved high enrichment scores in high-risk samples. Especially, loss-of-function antisense approach showed that DEGs between the predicted two clusters were metastasis-related. Conclusions The EMT-related gene pair signature can identify the high relapse-risk patients with stage II CRC, which can facilitate individualised management of patients.

Cancer stem cells, with unlimited self-renewal potential and other stem cell characteristics, occur in several types of cancer, including ovarian cancer (OvC). Although CSCs can cause tumor initiation, malignant proliferation, relapse and multi-drug resistance, ways to eliminate them remain unknown. In the present study, we compared ovarian cancer stem cell (OVCSC) expression profiles in normal ovarian surface epithelium and ovarian cells from patients with advanced disease to identify key pathways and specific molecular signatures involved in OVC progression and to prescreen candidate small-molecule compounds with anti-OVCSC activity. Comparison of genome-wide expression profiles of OvC stemness groups with non-stemness controls revealed 6495, 1347 and 509 differentially expressed genes in SDC, SP1 and SP2 groups, respectively, with a cut-off of fold-change set at >1.5 and P<0.05. NAB1 and NPIPL1 were commonly upregulated whereas PROS1, GREB1, KLF9 and MTUS1 were commonly downregulated in all 3 groups. Most differentially expressed genes consistently clustered with molecular functions such as protein receptor binding, kinase activity and chemo-repellent activity. These genes regulate cellular components such as centrosome, plasma membrane receptors, and basal lamina, and may participate in biological processes such as cell cycle regulation, chemoresistance and stemness induction. Key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as ECM receptor, ErbB signaling, endocytosis and adherens junction pathways were enriched. Gene co-expression extrapolation screening by the Connectivity Map revealed several small-molecule compounds (such as SC-560, disulfiram, thapsigargin, esculetin and cinchonine) with potential anti-OVCSC properties targeting OVCSC signature genes. We identified several key CSC features and specific regulation networks in OVCSCs and predicted several small molecules with potential anti-OVCSC pharmacological properties, which may aid the development of OVCSC-specific drugs.

Cervical cancer stem cells (CCSCs) are considered major causes of chemoresistance/radioresistance and metastasis. Although several cell surface antigens have been identified in CCSCs, these markers vary among tumors because of CSC heterogeneity. However, whether these markers specifically distinguish CCSCs with different functions is unclear. Here, we demonstrated that CCSCs exist in two biologically distinct phenotypes characterized by different levels of cytosolic phospholipase A2α (cPLA2α) expression. Overexpression of cPLA2α results in a CD44+CD24− phenotype associated with mesenchymal traits, including increased invasive and migration abilities, whereas CCSCs with cPLA2α downregulation express CD133 and show quiescent epithelial characteristics. In addition, cPLA2α regulates the reversible transition between mesenchymal and epithelial CCSC states through PKCζ, an atypical protein kinase C, which governs cancer cell state changes and the maintenance of various embryonic stem cell characteristics, further inhibiting β‐catenin‐E‐cadherin interaction in membrane and promoting β‐catenin translocation into the nucleus to affect the transcriptional regulation of stemness signals. We propose that reversible transitions between mesenchymal and epithelial CCSC states regulated by cPLA2α are necessary for cervical cancer metastasis and recurrence. Thus, cPLA2α might be an attractive therapeutic target for eradicating different states of CCSCs to eliminate tumors more effectively.

Background Stemness is defined as the potential of cells for self-renewal and differentiation. Many transcriptome-based methods for stemness evaluation have been proposed. However, all these methods showed low negative correlations with differentiation time and can’t leverage the existing experimentally validated stem cells to recognize the stem-like cells. Methods Here, we constructed a stemness index for single-cell samples (StemSC) based on relative expression orderings (REO) of gene pairs. Firstly, we identified the stemness-related genes by selecting the genes significantly related to differentiation time. Then, we used 13 RNA-seq datasets from both the bulk and single-cell embryonic stem cell (ESC) samples to construct the reference REOs. Finally, the StemSC value of a given sample was calculated as the percentage of gene pairs with the same REOs as the ESC samples. Results We validated the StemSC by its higher negative correlations with differentiation time in eight normal datasets and its higher positive correlations with tumor dedifferentiation in three colorectal cancer datasets and four glioma datasets. Besides, the robust of StemSC to batch effect enabled us to leverage the existing experimentally validated cancer stem cells to recognize the stem-like cells in other independent tumor datasets. And the recognized stem-like tumor cells had fewer interactions with anti-tumor immune cells. Further survival analysis showed the immunotherapy-treated patients with high stemness had worse survival than those with low stemness. Conclusions StemSC is a better stemness index to calculate the stemness across datasets, which can help researchers explore the effect of stemness on other biological processes.